TRIM35-mediated degradation of nuclear PKM2 destabilizes GATA4/6 and induces P53 in cardiomyocytes to promote heart failure.

Animals Mice Apoptosis Regulatory Proteins / metabolism GATA4 Transcription Factor / metabolism Heart Diseases / metabolism Heart Failure / metabolism Myocytes, Cardiac / metabolism Pyruvate Kinase / metabolism Transcription Factors / metabolism Tumor Suppressor Protein p53 / metabolism

Journal

Science translational medicine
ISSN: 1946-6242
Titre abrégé: Sci Transl Med
Pays: United States
ID NLM: 101505086

Informations de publication

Date de publication:
02 11 2022
Historique:
entrez: 2 11 2022
pubmed: 3 11 2022
medline: 5 11 2022
Statut: ppublish

Résumé

Pyruvate kinase M2 (PKM2) is a glycolytic enzyme that translocates to the nucleus to regulate transcription factors in different tissues or pathologic states. Although studied extensively in cancer, its biological role in the heart remains unresolved. PKM1 is more abundant than the PKM2 isoform in cardiomyocytes, and thus, we speculated that PKM2 is not genetically redundant to PKM1 and may be critical in regulating cardiomyocyte-specific transcription factors important for cardiac survival. Here, we showed that nuclear PKM2 (

Identifiants

DOI: 10.1126/scitranslmed.abm3565 PMID: 36322626
pubmed: 36322626
doi: 10.1126/scitranslmed.abm3565
doi:

Substances chimiques

Apoptosis Regulatory Proteins 0
Gata4 protein, mouse 0
GATA4 Transcription Factor 0
Pyruvate Kinase EC 2.7.1.40
Transcription Factors 0
TRIM35 protein, mouse 0
Tumor Suppressor Protein p53 0
Gata6 protein, mouse 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

eabm3565

Subventions

Organisme : CIHR
Pays : Canada

Auteurs

Maria Areli Lorenzana-Carrillo (MA)

Department of Medicine, University of Alberta, Edmonton, AB T6G 2R3, Canada.
Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB T6G 2B7, Canada.
Cardiovascular Research Centre, University of Alberta, Edmonton, AB T6G 1C9, Canada.
ORCID: 0000-0003-3268-7436

Keshav Gopal (K)

Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB T6G 2B7, Canada.
Cardiovascular Research Centre, University of Alberta, Edmonton, AB T6G 1C9, Canada.
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2H1, Canada.

Nikole J Byrne (NJ)

Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB T6G 2B7, Canada.
Cardiovascular Research Centre, University of Alberta, Edmonton, AB T6G 1C9, Canada.
Department of Pediatrics, University of Alberta, Edmonton, AB T6G 1C9, Canada.

Saymon Tejay (S)

Department of Medicine, University of Alberta, Edmonton, AB T6G 2R3, Canada.
Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB T6G 2B7, Canada.
Cardiovascular Research Centre, University of Alberta, Edmonton, AB T6G 1C9, Canada.
ORCID: 0000-0002-0641-041X

Bruno Saleme (B)

Department of Medicine, University of Alberta, Edmonton, AB T6G 2R3, Canada.
Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB T6G 2B7, Canada.
Cardiovascular Research Centre, University of Alberta, Edmonton, AB T6G 1C9, Canada.
ORCID: 0000-0003-4488-9545

Subhash K Das (SK)

Department of Medicine, University of Alberta, Edmonton, AB T6G 2R3, Canada.
Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB T6G 2B7, Canada.
Cardiovascular Research Centre, University of Alberta, Edmonton, AB T6G 1C9, Canada.

Yongneng Zhang (Y)

Department of Medicine, University of Alberta, Edmonton, AB T6G 2R3, Canada.
Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB T6G 2B7, Canada.
Cardiovascular Research Centre, University of Alberta, Edmonton, AB T6G 1C9, Canada.
ORCID: 0000-0002-0791-9381

Alois Haromy (A)

Department of Medicine, University of Alberta, Edmonton, AB T6G 2R3, Canada.
Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB T6G 2B7, Canada.
Cardiovascular Research Centre, University of Alberta, Edmonton, AB T6G 1C9, Canada.
ORCID: 0000-0003-4744-9879

Farah Eaton (F)

Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB T6G 2B7, Canada.
Cardiovascular Research Centre, University of Alberta, Edmonton, AB T6G 1C9, Canada.
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2H1, Canada.

Michelle Mendiola Pla (M)

Department of Surgery, Duke University, Durham, NC 27710, USA.
ORCID: 0000-0001-9348-7708

Dawn E Bowles (DE)

Department of Surgery, Duke University, Durham, NC 27710, USA.
ORCID: 0000-0002-2781-1300

Jason R B Dyck (JRB)

Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB T6G 2B7, Canada.
Cardiovascular Research Centre, University of Alberta, Edmonton, AB T6G 1C9, Canada.
Department of Pediatrics, University of Alberta, Edmonton, AB T6G 1C9, Canada.

John R Ussher (JR)

Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB T6G 2B7, Canada.
Cardiovascular Research Centre, University of Alberta, Edmonton, AB T6G 1C9, Canada.
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2H1, Canada.

Evangelos D Michelakis (ED)

Department of Medicine, University of Alberta, Edmonton, AB T6G 2R3, Canada.
Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB T6G 2B7, Canada.
Cardiovascular Research Centre, University of Alberta, Edmonton, AB T6G 1C9, Canada.
ORCID: 0000-0003-0787-7721

Gopinath Sutendra (G)

Department of Medicine, University of Alberta, Edmonton, AB T6G 2R3, Canada.
Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB T6G 2B7, Canada.
Cardiovascular Research Centre, University of Alberta, Edmonton, AB T6G 1C9, Canada.
Cancer Research Institute of Northern Alberta, University of Alberta, Edmonton, AB T6G 2E1, Canada.
ORCID: 0000-0002-8181-1483

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › TRIM35-mediated degradation of nuclear PKM2...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › TRIM35-mediated degradation of nuclear PKM2...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines régulatrices de l'apoptose › TRIM35-mediated degradation of nuclear PKM2...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription GATA › Facteur de transcription GATA-4 › TRIM35-mediated degradation of nuclear PKM2...
questionsmedicales.fr › Maladies cardiovasculaires › Cardiopathies › TRIM35-mediated degradation of nuclear PKM2...
questionsmedicales.fr › Maladies cardiovasculaires › Cardiopathies › Défaillance cardiaque › TRIM35-mediated degradation of nuclear PKM2...
questionsmedicales.fr › Cellules › Cellules musculaires › Myocytes cardiaques › TRIM35-mediated degradation of nuclear PKM2...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Phosphotransferases › Phosphotransferases (Alcohol Group Acceptor) › Pyruvate kinase › TRIM35-mediated degradation of nuclear PKM2...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › TRIM35-mediated degradation of nuclear PKM2...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Phosphoprotéines › Protéine p53 suppresseur de tumeur › TRIM35-mediated degradation of nuclear PKM2...